Author(s)

Shintaro Ishiyama^1*, Yoshiya Asano², Minoru Suzuki³, Mitsuru Akashi⁴, Hiroshi Shimoda^2,5

¹Faculty of Science and Technology, Graduate School of Science and Technology, Hirosaki University, Bunkyo, Hirosaki, Aomori, Japan.
²Department of Neuroanatomy, Cell Biology and Histology, Graduate School of Medicine, Hirosaki University, Zaifu, Hirosaki, Aomori, Japan.
³Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, Asahiro-Nishi, Kumamori, Sennan, Osaka, Japan.
⁴Building Block Science, Graduate School of Frontier Biosciences, Osaka University, Yamada-Oka, Osaka, Japan.
⁵Department of Anatomical Science, Graduate School of Medicine, Hirosaki University, Hirosaki, Zaifu, Hirosaki, Aomori, Japan.

Boron neutron capture therapy (BNCT) is based on the incorporation of boron-containing drugs to cancer cells and the nuclear reaction of ¹⁰B atoms by thermal neutron irradiation results in tumor degeneration. For the development of this therapy, currently, long time and high cost consuming experiments using many animals are required. In this study, we constructed a new in vitro evaluation system for BNCT by combination of an artificial tumor tissue model, comprised of normal human dermal-derived fibroblast (NHDF) and human pancreatic cancer cell line BxPC3, and the optical plastic material CR-39 as a solid state nuclear track detector. Administration of boronophenylalanine (¹⁰BPA) as a boron-containing drug and neutron irradiation up to 2.52 × 10¹² n/cm² to the control tissue constructed by NHDF (NHDF3D) and BxPC3 cell loaded tissue (NHDF3D/BxPC3) resulted in detection of 1.6 times higher number of α-ray/recoiled Li particle tracks in NHDF3D/BxPC3 in comparison to NHDF3D, demonstrating that putative irradiation damage to cancer cells can be evaluated by this system. On a cellular level, the hit number of α-ray/recoiled Li particle tracks per single BxPC3 cells and NHDF was evaluated as 5.46 and 1.71, respectively. The tumor and normal tissue ratio (T/N ratio) was 3.19, which was corresponded with those of BPA as 2 - 4 that reported in the previous studies. This new in vitro evaluation system may provide a useful tool for a low cost, labor-saving, and non-animal method for the development of new boron-containing drugs or improvement of BNCT conditions.

Boron Neutron Capture Therapy (BNCT), Boronophenylalanine (¹⁰BPA), Artificial Human Tumor Tissue Model, Cell Accumulation Method

Ishiyama, S. , Asano, Y. , Suzuki, M. , Akashi, M. and Shimoda, H. (2019) In Vitro Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model. Journal of Cancer Therapy, 10, 835-845. doi: 10.4236/jct.2019.1010071.